Critical care explorations最新文献

Objective: To identify distinct phenotypes of acute respiratory distress syndrome (ARDS) developing after hematopoietic cell transplantation (HCT), using routinely available clinical data at ICU admission.

Design: Multicenter retrospective cohort study using latent class analysis.

Setting: ICUs across three Mayo Clinic campuses (Minnesota, Florida, and Arizona).

Patients: A total of 166 adult patients who developed ARDS within 120 days following HCT (96 allogeneic, 70 autologous).

Intervention: None.

Measurements and main results: Model selection was based on multiple metrics including Bayesian information criteria, entropy, and Vuong-Lo-Mendell-Rubin Likelihood Ratio testing. A two-class model optimally described the cohort. Class 1 (n = 81) was characterized by worse hypoxemia (P/F ratio 157 vs. 210, p = 0.002), higher Pco2 (41 vs. 36 mm Hg, p < 0.001), and higher bilirubin (1.4 vs. 0.9 mg/dL, p < 0.001) compared with class 2 (n = 85). Both classes included a mix of transplant types, transcending a simple autologous/allogeneic dichotomy, although class 1 had more allogeneic recipients (70.4% vs. 45.9%, p = 0.001). Although time-from-transplant was not a class-defining variable, class 1 occurred later after transplant (30.0 vs. 11.9 d, p < 0.001) with higher frequency of idiopathic pneumonia syndrome (14.8% vs. 2.4%, p = 0.004). Class 2 had more frequent neutropenia (leukocytes 0.4 vs. 5.9 × 109, p < 0.001) and higher frequency of peri-engraftment respiratory distress syndrome (29.4% vs. 9.9%, p = 0.005). Outcomes were significantly worse for class 1 (90-d mortality: 72.8% vs. 48.2%, p = 0.001). An exploratory parsimonious model had good classification accuracy (0.90) using just six variables: leukocyte count, platelet count, bilirubin, Pco2, body mass index, and temperature.

Conclusions: ARDS after HCT comprises two distinct phenotypes with distinct clinical characteristics and outcomes. These phenotypes align with recognized post-HCT lung injury syndromes and may reflect different underlying biological processes. This framework provides a foundation for investigating targeted therapeutic approaches.

Objective: This post hoc study of the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECT) III trial investigates whether improving traumatic brain injury (TBI) classification, using serum biomarkers (glial fibrillary acidic protein [GFAP] and ubiquitin carboxyl-terminal esterase L1 [UCH-L1]) and algorithmically assessed total lesion volume, could identify a subset of responders to progesterone treatment, beyond broad measures like the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale-Extended (GOS-E), which may fail to capture subtle changes in TBI recovery.

Design: Brain lesion volumes on CT scans were quantified using Brain Lesion Analysis and Segmentation Tool for CT. Patients were classified into true-positive and true-negative groups based on an optimization scheme to determine a threshold that maximizes agreement between radiological assessment and objectively measured lesion volume. True-positives were further categorized into low (> 0.2-10 mL), medium (> 10-50 mL), and high (> 50 mL) lesion volumes for analysis with protein biomarkers and injury severity. Correlation analyses linked Rotterdam scores (RSs) with biomarker levels and lesion volumes, whereas Welch's t-test evaluated biomarker differences between groups and progesterone's effects.

Setting: Forty-nine level 1 trauma centers in the United States.

Patient: Patients with moderate-to-severe TBI.

Interventions: Progesterone.

Measurements and main results: GFAP and UCH-L1 levels were significantly higher in true-positive cases with low to medium lesion volume. Only UCH-L1 differed between progesterone and placebo groups at 48 hours. Both biomarkers and lesion volume in the true-positive group correlated with the RS. No sex-specific or treatment differences were found.

Conclusions: This study reaffirms elevated levels of GFAP and UCH-L1 as biomarkers for detecting TBI in patients with brain lesions and for predicting clinical outcomes. Despite improved classification using CT-imaging segmentation and serum biomarkers, we did not identify a subset of progesterone responders within 24 or 48 hours of progesterone treatment. More rigorous and quantifiable measures for classifying the nature of injury may be needed to enable development of therapeutics as neither serum markers nor algorithmic CT analysis performed better than the older metrics of Rotterdam or GCS metrics.

Importance: The relationship between endotoxin activity, organ failure, and mortality is not well understood.

Objective: To test whether the combination of endotoxin activity and organ failure identifies patients at higher risk of death from sepsis and determine the relationship to previously described sepsis phenotypes.

Design, setting, and participants: Prospective observational study in four ICUs enrolling critically ill patients with septic shock.

Main outcomes and measures: Endotoxin activity assay (EAA) results, Sequential Organ Failure Assessment (SOFA), and multiple organ dysfunction (MODS) and 28-day mortality.

Results: We enrolled 90 patients aged 25-95 years and set an EAA cutoff of greater than or equal to 0.6 together with SOFA greater than 11 or MODS greater than 9 to define endotoxic septic shock (ESS). At baseline mean EAA was 0.64 (sd = 0.19), whereas mean SOFA and MODS were 10.3 (sd 3.2) and 5.8 (sd 3.1), respectively. EAA greater than or equal to 0.6 and SOFA greater than 11 were present in 20 patients (23.3%) and these patients had 60% mortality. EAA greater than or equal to 0.6 and SOFA less than or equal to 11 occurred in 31 (36.0%) with mortality 12.9%. Of the 35 remaining patients with EAA less than 0.6, 29 (33.7%) had SOFA less than or equal to 11 and 5 of them (17.2%) died. Only six patients (7.0%) had EAA less than 0.6 and SOFA greater than 11 and none died (p < 0.001). All patients with MODS greater than 9 also had EAA greater than or equal to 0.6 (12 patients) with 75% mortality. EAA greater than or equal to 0.6 with MODS less than or equal to 9 occurred in 39 patients with 17.9% mortality (p < 0.001). ESS (EAA ≥ 0.6 together with SOFA > 11 or MODS > 9) occurred in 21 patients and they had significantly higher mortality (57.1% vs. 15.9%, p < 0.001) compared with non-ESS, with a relative risk for death of 3.58 (95% CI, 1.86-6.91). Among ESS patients, 7 (33.3%) had δ phenotype, whereas only 4 (5.8%) had δ among non-ESS (p = 0.001).

Conclusions and relevance: ESS compromises patients with the highest mortality rate from sepsis. Such patients are most appropriate for trials testing anti-endotoxin therapy for improving survival.

Importance: Accurate and reliable sedation assessment is crucial to improving patient outcomes in the ICU.

Objective: To evaluate the inter-rater agreement and reliability of Richmond Agitation Sedation Scale (RASS) assessments between bedside nurses and trained investigators in patients receiving mechanical ventilation in the ICU.

Design, setting, and participants: An assessor triad, comprising an ICU nurse providing direct patient care and two trained investigators, simultaneously performed RASS assessments during 79 encounters with 62 unique patients receiving mechanical ventilation at two ICUs at a tertiary care academic hospital in Colorado. A total of 58 nurses participated in the study.

Main outcomes and measures: The inter-rater reliability of RASS assessments was evaluated with the intraclass correlation coefficient (ICC) and weighted kappa (κ), and inter-rater agreement was evaluated with percentage agreement and Bland-Altman analysis.

Results: Acute respiratory failure (55%) and altered mental status (21%) were the most common reasons for mechanical ventilation. Most patients were receiving one (interquartile range, 0.5-2) continuous sedative during the assessment. The inter-rater reliability of RASS assessments between the nurses and investigators (ICC, 0.728-0.779; weighted κ, 0.62-0.63) was lower than between the two investigators (ICC, 0.891; weighted κ, 0.80). The assessor triad agreed on the same RASS values in only 35% of observations. The average differences in RASS were greater between the investigators and nurses, ranging from -0.658 to -0.544, compared with 0.114 between the two investigators. Compared with the mean of the two investigators, RASS values recorded by nurses were more likely to be higher (52% of observations), indicating a lighter sedation level. In 16% of observations, at least one assessor commented on uncertainty or ambiguity with the RASS.

Conclusions and relevance: The inter-rater reliability of RASS assessments was high. However, we observed variations in the degree of agreement by assessor category. Further studies are necessary to explore how factors such as assessor characteristics, ICU environment, and patient conditions influence the inter-rater agreement of the RASS in contemporary ICU practices.

Objectives: We sought to estimate the association between chronic use of renin-angiotensin system inhibitors and acute kidney injury requiring renal replacement therapy in critically ill adult patients with sepsis.

Design: Population-based cohort study in Ontario, Canada.

Setting: ICUs in Ontario, Canada, between April 2008 and March 2019.

Patients: Elderly patients admitted to an ICU with a sepsis diagnosis; we excluded patients with established indications of renin-angiotensin system inhibitors.

Interventions: The prior use (i.e., within 100 d of hospitalization) of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker served as the main exposure of interest; the active comparator was the prior use of calcium channel blockers.

Measurements and main results: Acute kidney injury requiring renal replacement therapy was the primary outcome. Septic shock and all-cause mortality at 30 days served as secondary outcomes. We fitted multivariable modified Poisson regression models to adjust for potential confounders; associations were reported as risk ratios (RRs) alongside 95% CIs. We included 8621 patients, of whom 81% received a renin-angiotensin system inhibitor; mean age was 78 years. Renal replacement therapy was performed in 3.2% of patients; compared with the prior use of a calcium channel blocker, prior use of a renin-angiotensin system inhibitor was associated with a higher risk of acute kidney injury and renal replacement therapy (RR, 1.57; 95% CI, 1.10-2.24), septic shock (RR, 1.18; 95% CI, 1.04-1.33), but not all-cause mortality at 30 days (RR, 0.93; 95% CI, 0.88-1.01). Our results were robust across sensitivity analyses.

Conclusions: Chronic use of a renin-angiotensin system inhibitor is associated with a higher risk of renal replacement therapy and septic shock in adult patients with sepsis.

Importance: Vasopressin is used in one-third of patients with septic shock to augment hemodynamics and reduce overall catecholamine exposure. However, the optimal clinical context in which to initiate vasopressin is unknown.

Objectives: To determine the association between norepinephrine-equivalent dose, lactate concentration, and time duration from shock onset at vasopressin initiation with in-hospital mortality.

Design, setting, and participants: Retrospective, observational evaluation utilizing Medical Information Mart for Intensive Care-IV and electronic ICU Collaborative Research Database databases of adult patients with septic shock based on modified Sepsis-3 criteria receiving continuous infusion catecholamines.

Main outcomes and measures: The associations of norepinephrine-equivalent dose, lactate concentration, and time duration from shock onset at vasopressin initiation with in-hospital mortality were evaluated with multivariable regression models.

Results: In total, 1409 patients from 209 hospitals were included. At vasopressin initiation patients had a median (interquartile range) norepinephrine-equivalent dose 28.4 µg/min (16.4-42.6 µg/min), lactate concentration 3.7 mmol/L (2.5-6.2 mmol/L), and 5.6 hours (2.0-13.5 hr) had elapsed since shock onset. All three variables of interest were associated with in-hospital mortality. Three restricted cubic spline knots were identified where the relationship between norepinephrine-equivalent dose and in-hospital mortality changed substantially: 9, 28, and 72 µg/min. The odds of in-hospital mortality increased by 90% and 3.9-fold when comparing vasopressin initiation at norepinephrine-equivalent doses of 28 µg/min and 72 µg/min to 9 µg/min, respectively (adjusted odds ratio [OR], 1.90 [95% CI, 1.49-2.41] and 3.93 [95% CI, 2.74-5.64]). The odds of in-hospital mortality increased by 16% for every mmol/L in the lactate concentration at vasopressin initiation (adjusted OR, 1.16 [95% CI, 1.11-1.21]). Finally, the odds of in-hospital mortality increased by 3% for every hour in the time duration from shock onset to vasopressin initiation (adjusted OR, 1.03 [95% CI, 1.01-1.04]).

Conclusions and relevance: Earlier adjunctive vasopressin initiation may decrease mortality in patients with septic shock.

Objectives background: Delirium remains frequently undetected by healthcare providers; partnering with family may be a novel way to identify and manage delirium. This study explores the feasibility of a family-administered intervention for delirium prevention, detection, and management.

Design: Pilot randomized controlled trial.

Setting: Two Canadian ICUs.

Subjects: Patient-family pairs (dyads) were included. Eligible patients had no primary brain injury, a Richmond Agitation-Sedation Scale score of greater than or equal to -3, and were expected to remain in the ICU for at least 24 hours to complete all study assessments.

Interventions: Dyads were randomly assigned to either standard care (control) or the intervention, which included delirium education and family-administered checklists with prevention/management strategies and a detection tool ("Sour Seven").

Measurements and main results: Outcomes included feasibility indicators, enrollment and completion rates, and psychological outcomes (Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and the Kessler Psychologic Distress (K-10) scales in the ICU and at 1- and 3-month follow-ups. Between January 2020 and June 2023, during the height of the COVID pandemic, 197 patient-family pairs were approached, with 64 (32%) consenting to participate; participation required both the patient and a family member. Despite recruitment challenges, 75% of families completed in-ICU questionnaires, and 38% completed all follow-ups. The family members in the intervention group demonstrated increased delirium knowledge compared with baseline delirium knowledge, and engagement in prevention strategies, with 8 of 19 (42%) family members identifying delirium using the Sour Seven. At the 3-month follow-up, seven family members showed significant anxiety, and five showed significant depression. Observations of ICU rounds revealed limited delirium discussions.

Conclusions: This pilot study demonstrated the feasibility of family-administered delirium care in ICU settings. However, the likely impact of the COVID-19 pandemic cannot be overlooked. The study faced recruitment challenges and demonstrated the difficulties of family involvement in delirium care, particularly during restricted family presence. A full evaluation of effectiveness requires a hypothesis-testing trial with procedural adjustments to streamline data collection and strengthen family-care team partnerships.

Trial registration: Clinicaltrials.gov (NCT04099472).

Importance: The vascular endothelial growth factor (VEGF) signaling pathway is important in the pathogenesis of acute respiratory distress syndrome (ARDS) with supportive genetic and proteomic evidence. Genetic polymorphisms within FLT1, which encodes VEGF receptor 1, associate with risk of ARDS in sepsis. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is a secreted splice variant of FLT1 that acts as a potent antagonist to circulating VEGF.

Objectives: To assess the association between early plasma concentrations of sFlt-1 and risk of ARDS and to determine if ARDS mediates the relationship between sFlt-1 and mortality during sepsis.

Design, setting, and participants: In a prospective cohort study, we enrolled 198 critically ill patients with sepsis per Sepsis-2 criteria. ARDS was defined per Berlin criteria.

Main outcomes and measures: Levels of sFlt-1 were quantified using electrochemiluminescence on plasma collected in the emergency department upon admission. We tested the association between plasma levels of sFlt-1 with ARDS and mortality using logistic regression adjusting for age, sex, and pulmonary versus nonpulmonary source of sepsis. We applied causal mediation analysis to determine the percentage of the total effect of sFlt-1 on mortality that was mediated by ARDS.

Results: We enrolled 198 patients; ARDS developed within 6 days in 29%. Plasma levels of sFlt-1 were significantly associated with risk of ARDS in sepsis (odds ratio [OR], 1.91 per log increase; 95% CI, 1.31-2.76 per log increase; p < 0.01). Plasma sFlt-1 levels were also associated with mortality (OR, 2.19 per log increase; 95% CI, 1.57-3.08 per log increase; p < 0.01). ARDS mediated 20.3% (95% CI, 6.9-98.1%) of the total effect of sFlt-1 on mortality (p < 0.01).

Conclusions and relevance: Higher plasma levels of sFlt-1 were associated with an increased risk of ARDS and ARDS mediated a significant proportion of the sFlt-1-associated mortality observed during sepsis. Our findings further implicate dysregulated VEGF signaling in ARDS and suggest that plasma sFlt-1 merits further investigation as an early endothelial therapeutic target for sepsis-associated ARDS and mortality.

Objectives: To conduct a systematic review and meta-analysis to determine if objective sedation monitoring practices reduce duration of mechanical ventilation and other clinical and healthcare utilization outcomes in critically ill adult patients.

Data sources: Ovid MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library and PROSPERO, and the grey literature.

Study selection: Observational or interventional original research studies, conducted in adult critically ill patients undergoing invasive mechanical ventilation, evaluating any objective sedation monitoring practice (e.g., electroencephalography [EEG]), and reporting on duration of mechanical ventilation or other secondary outcomes (e.g., length of stay) were included.

Data extraction: Meta-analysis was performed for pooled estimates of the primary outcome and each individual secondary outcome using random-effects modeling.

Data synthesis: Twenty studies (3410 patients) were included with 15 studies evaluating processed EEG monitoring, 2 evaluating EEG monitoring, and 3 evaluating processed facial electromyography (EMG). Processed EEG was not associated with reduced duration of mechanical ventilation (standardized mean difference [SMD] -0.33; 95% CI, -0.91 to 0.25; I2 = 84.4%). Secondary outcomes of processed EEG monitoring showed decreased hospital length of stay (days) (SMD -0.89; 95% CI, -1.17 to -0.62; I2 = 13.4%), reduced total sedative dose (reported in propofol equivalents, mg) (SMD -1.29; 95% CI, -2.27 to -0.31; I2 = 96.6%), and reduced total opioid dose (reported in morphine equivalents, mg) (SMD -0.40; 95% CI, -0.76 to -0.04; I2 = 77.0%). Processed facial EMG was associated with an increased risk of adverse events (risk ratio 1.40; 95% CI, 1.03-1.90; I2 = 0.00%). Risk of bias was serious for 65% (n = 13/20) of included studies.

Conclusions: Processed EEG monitoring is not associated with reduced duration of mechanical ventilation but may be associated with reduced sedative and opioid exposure and decreased hospital length of stay. Processed facial EMG monitoring may be associated with increased adverse events.

Importance: There is a large discrepancy between need and access to critical care in low- and middle-income countries. Little is known about what subgroups of patients are being prioritized for critical care.

Objectives: The primary objective was to assess what clinical, demographic, and socioeconomic variables were associated with timely ICU admission. Secondary objectives included determining the rate of ICU admission among patients who met admission criteria, inpatient mortality, and length of stay.

Design: Prospective cohort study.

Setting and participants: All adult patients meeting ICU admission criteria at the University Teaching Hospital of Butare, Huye, Rwanda.

Main outcomes and measures: The primary outcome was the proportion of patients admitted to ICU within 24 hours of being identified as critically ill. A multivariable logistic regression model was used to assess whether clinical, demographic, or socioeconomic factors are associated with timely ICU admission. Secondary outcomes were the proportion of patients admitted to ICU at any time, inpatient mortality, and length of stay.

Results: Three hundred eighteen patients were enrolled between January 24, 2024, and June 3, 2024. Eighty-eight (27.7%) were admitted to ICU within 24 hours. Requiring ICU for postoperative recovery (odds ratio [OR], 8.21; 95% CI, 3.64-19.8), obstetric patients (OR, 2.43; 95% CI, 0.92-6.41), and ICU bed availability (OR, 1.26; 95% CI, 1.02-1.55) increased the odds of timely ICU admission in multivariable analysis. Socioeconomic status, gender, and social connections had minimal association with ICU admission, with wide CIs. The inpatient mortality rate was 44.0% and average length of stay was 14 days.

Conclusions and relevance: Obstetric and postoperative patients are prioritized for ICU admission. There is a large unmet need for critical care in Rwanda, and mortality among critically ill patients is high.